Sitagliptin (Compound I) is the international commonly accepted name for 7-[(3R)-3-amino-1-oxo-4-(2,4,5-trifluorophenyl)butyl]-5,6,7,8-tetrahydro-3-(trifluoromethyl)-1,2,4-triazolo[4,3-a]pyrazine (which is also known as (2R)-4-oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl]-1-(2,4,5-trifluorophenyl)butan-2-amine), and has an empirical formula of C16H15F6N5O and a molecular weight of 407.31.

The phosphate salt of sitagliptin has been selected for medical purposes since has been proved to be useful for the treatment of diabetes. Sitagliptin phosphate is a selective inhibitor of dipeptidyl peptidase IV which lowers blood sugar levels in patients with Type 2 diabetes, also known as non-insulin dependent diabetes mellitus. In the United States, sitagliptin phosphate is marketed under the name Januvia™ for the treatment of Type 2 diabetes.
Sitagliptin phosphate salt and different forms thereof have been disclosed in a number of references (i.e. U.S. Pat. No. 7,326,708, and U.S. Patent Application Nos. 20060287528, 20070021430 and 20070281941).
Sitagliptin base and its pharmaceutically acceptable acid addition salts have been described in U.S. Pat. No. 6,699,871. In particular, Example 7 of U.S. Pat. No. 6,699,871 discloses the preparation of sitagliptin base and its hydrochloride salt.
Different salt forms of the same pharmaceutically active moiety differ in their physical properties such as melting point, solubility, etc. These properties may appreciably influence pharmaceutical properties such as dissolution rate and bioavailability. In addition, polymorphism, which is defined as the ability of a substance to crystallize in more than one crystal lattice arrangement, can also influence many aspects of solid state properties of a drug. Different crystal modifications of a substance may differ considerably from one another in many respects such as their solubility, dissolution rate and finally bioavailability.
In this regard, International Patent Publication No. WO 05/072530 described several novel crystalline salts of sitagliptin, i.e. the hydrochloric acid, tartaric acid, benzenesulfonic acid, p-toluenesulfonic acid, and 10-camphorsulfonic acid crystalline salts. In addition, the hemifumarate salt of sitagliptin has been described by D. Kim et al. in J. Med. Chem. 2005, 48, 141-151. Also, International Patent Publication No. WO 07/035198 relates to a crystalline anhydride form of the dodecylsulfate salt of sitagliptin. Furthermore, International Patent Publication No. WO 08/000418 discloses the preparation of sitagliptin hydrochloride in amorphous form. In addition, International Patent Publication No. WO 09/085990 describes other acid addition salts of sitagliptin, i.e. sitagliptin salts of di-p-tolyl-L-tartaric acid, phosphoric acid, sulfuric acid, hydrobromic acid, methanesulfonic acid, acetic acid, benzoic acid, oxalic acid, succinic acid, mandelic acid, fumaric acid, and lactic acid.
In view of the foregoing, it would be desirable to provide new salt forms of sitagliptin. Further, it would be desirable to have reliable processes for producing these salt forms of sitagliptin. Additionally, the various salt forms of sitagliptin could be used to prepare improved pharmaceutical compositions.